Developmental and sex differences in cadmium distribution and metallothionein induction and localization

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Abstract
Age‐ and sex‐related differences in hepatic and renal distribution of cadmium (Cd) and the effect of Cd injection (10 μmol/kg) on tissue zinc (Zn), copper (Cu) and metallothionein (MT) levels were investigated in 2‐ to 84‐day old rats. Renal Cd accumulation increased with age of the animal. Sex differences in renal Cd accumulation were noted in young animals where the 2‐ and 8‐day old males had significantly greater concentration than the females. There were no clear effects of Cd on renal Zn. Renal Cu levels, however, were elevated in the adults. The adult females contained about twice as much MT as the adult males. Cd treatment had no effect on renal MT levels of 8‐ to 84‐day old animals but depressed the levels in 2‐day old. Age‐related increase in hepatic Cd accumulation was also found; the pattern was more clear cut in females than in males. In addition, in the females the hepatic Cd concentration was significantly higher than in the males. Cd‐injection significantly increased hepatic Zn and MT concentrations only in weaned animals. While there were no sex differences in MT levels in the young animals, the weaned females had significantly more MT than the corresponding males. Immunohistochemical staining for MT showed positive staining in both cytoplasm and nuclei of the parenchymal cells. The number of MT‐positive nuclei was dependent on the relative MT concentration of the liver. In spite of the intense nuclear staining in 2‐day old controls and 84‐day old Cd‐injected rats, less than 1% of the hepatic MT was present in the nuclear fraction. The above data on the tissue distribution of Cd point to the possible effects of sex hormones on Cd metabolism. The results of the intracellular distribution of MT suggest that nuclear MT represents only a minute fraction of the total cellular MT, even in the neonatal rat.